scholarly journals SRSF2 mutations in epithelial ovarian cancer

2017 ◽  
Vol 5 (3) ◽  
pp. 25-29 ◽  
Author(s):  
Milena Sabrina Nicoloso ◽  
Monica Schiappacassi ◽  
Alessandra Dall’Acqua ◽  
Sara D’Andrea ◽  
Sara Benevol ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Alternative Splicing ◽  
Epithelial Ovarian Cancer ◽  
Splicing Factor ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Apoptotic Response ◽  
Apoptotic Protein ◽  
Platinum Chemotherapy ◽  
Protein Variants

Resistance to platinum chemotherapy regimens represents a major obstacle in the successful treatment of epithelial ovarian cancer (EOC) patients. Among the molecular mechanism responsible for resistance to platinum, alternative splicing, which is induced upon platinum treatment, can control apoptosis by regulating the expression of apoptotic protein variants with opposite functions. Alterations in alternative splicing are found in tumors and can hinder apoptotic response. In the present study we sequenced SRSF2, a splicing factor that regulates Caspase-8 and Caspase-9 variants, in search of mutations that could possibly explain alternative mechanisms of platinum resistant in EOC.

scholarly journals Snail Driving Alternative Splicing of CD44 by ESRP1 Enhances Invasion and Migration in Epithelial Ovarian Cancer

2017 ◽  
Vol 43 (6) ◽  
pp. 2489-2504 ◽  
Author(s):  
Le Chen ◽  
Ying Yao ◽  
Lijuan Sun ◽  
Jiajia Zhou ◽  
Minmin Miao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Alternative Splicing ◽  
Epithelial Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Regulatory Protein ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: Our study aims to investigate the role, effect and mechanisms of ESRP1 (epithelial splicing regulatory protein 1) in epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). Methods: Microarray and immunohistochemical analysis of ESRP1 expression were performed in EOC cases. The correlations between ESRP1 expression and clinical factors on EOC were assessed. Lentivirus-mediated RNA interference and EGFP vector which contains ESRP1 gene were used to down-regulate and up-regulate ESRP1 expression in human EOC cell lines. Roles of ESRP1 in cell growth, migration and invasion of EOC cells were also measured by Cell Counting Kit-8 and Transwell systems in vitro and by a nude mice intraperitoneal transplantation model in vivo. Results: By the analysis of Gene Expression Omnibus (GEO) (p<0.05) and our own microarray data (p<0.001), ESRP1 expression in EOC was significantly different from normal ovarian tissue. It was abundant in the nuclei of cancer cells and in malignant lesions. However, it was weakly expressed or negative in both normal and benign lesions. High ESRP1 expression in EOC was associated with poor clinical outcomes. Decreased ESRP1 expression significantly increased cell migration and invasion both in vivo and in vitro. Snail strongly repressed ESRP1 transcription through binding to the ESRP1 promoter in EOC cells. Furthermore, ESRP1 regulated the expression of CD44s. Down-regulated ESRP1 resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition (EMT) program in EOC. Up-regulatin of ESRP1 was detected in mesenchymal to epithelial transition (MET) in vivo. Conclusions: ESRP1 regulates CD44 alternative splicing during the EMT process which plays an important role in EOC carcinogenesis. In addition, ESRP1 is associated with disease prognosis in EOC.

Second-line Intraperitoneal Platinum-based Therapy Leads to an Increase in Second-line Progression-free Survival for Epithelial Ovarian Cancer

2016 ◽  
Vol 26 (4) ◽  
pp. 626-631 ◽  
Author(s):  
Michelle M. Boisen ◽  
Jamie L. Lesnock ◽  
Scott D. Richard ◽  
Sushil Beriwal ◽  
Joseph L. Kelley ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Primary Response ◽  
Published Data ◽  
Second Line ◽  
First Recurrence ◽  
Oncology Practice ◽  
Platinum Chemotherapy

ObjectiveOnly 3% of patients with epithelial ovarian cancer (EOC) have a longer treatment-free interval (TFI) after second-line intravenous (IV) platinum chemotherapy than with frontline IV therapy. We sought to examine what impact second-line combination IV/intraperitoneal (IV/IP) platinum therapy might have on the ratio of second-line to first-line TFI in patients treated with second-line IP platinum chemotherapy for first recurrence after front-line IV therapy.MethodsA retrospective analysis of women who received combination platinum-based IV/IP chemotherapy for recurrent EOC between January 2005 and March 2011 was conducted. Patients were identified from the tumor registry, and office records from a large gynecologic oncology practice and patient records were reviewed. The first and second TFIs were defined as the time from the end of previous platinum-based therapy to the start of next therapy.ResultsTwenty-five women received IV/IP chemotherapy for their first EOC recurrence after IV chemotherapy. In 10 patients (40%), we observed a longer TFI after IV/IP chemotherapy than after primary IV chemotherapy. For these 10 patients, the median TFI for primary response was 22 months (range, 15–28), whereas median TFI after IV/IP chemotherapy for recurrent disease was 37 months (range, 12–61).ConclusionsFor EOC patients with limited peritoneal recurrence, 40% of patients had a second-line IP-platinum TFI that exceeded their frontline IV-platinum TFI compared to published data. These data support the use of IV/IP chemotherapy as a treatment for recurrence.

Single CpG island methylation is not sufficient to maintain the silenced expression of CASPASE-8 apoptosis-related gene among women with epithelial ovarian cancer

2014 ◽  
Vol 68 (1) ◽  
pp. 87-91 ◽  
Author(s):  
Letícia da Conceição Braga ◽  
Luciana Maria Silva ◽  
Ana Paula Álvares da Silva Ramos ◽  
Josiane Barbosa Piedade ◽  
Paula Vieira Teixeira Vidigal ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cpg Island ◽  
Caspase 8 ◽  
Related Gene ◽  
Cpg Island Methylation ◽  
Apoptosis Related Gene

A phase I study of veliparib incorporated into front-line platinum based cheotherpy and bevacizumab in epithelial ovarian cancer (NCT00989651): A GOG/nrg trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5523-5523 ◽  
Author(s):  
Deborah Kay Armstrong ◽  
Kathleen N. Moore ◽  
Austin Miller ◽  
Katherine M. Bell-McGuinn ◽  
Russell J. Schilder ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Residual Disease ◽  
Maximum Tolerated Dose ◽  
Phase Iii ◽  
Front Line ◽  
Polymerase Inhibitor ◽  
Recommended Phase Ii Dose ◽  
Platinum Chemotherapy ◽  
Data Informed

5523 Background: Veliparib, a poly-(ADP-ribose)-polymerase inhibitor, increases anti-tumor activity when combined with platinum chemotherapy and has monotherapy activity in BRCA deficient tumors. This study was done to determine the recommended phase II dose (RP2D) of veliparib in combination with front line treatment for epithelial ovarian cancer (EOC). Methods: Eligible patients had newly diagnosed, stage II-IV EOC. Six regimens were evaluated, 3 variations of chemo delivery with either continuous (D1-21) or intermittent (days-2-5) veliparib BID. Chemo included 1: IV q3week carboplatin (C) (AUC 6) and paclitaxel(T) (175mg/m2); 2, IV q3week C (AUC 6) and weekly T(80mg/m2); and 3, IV T (135mg/m2, day 1), IP cisplatin (75mg/m2, day 1 or 2) and IP T (60mg/m2, day 8). Bevacizumab 15mg/kg started cycle 2 and continued as monotherapy cycles 7-22. A 3+3 dose escalation design evaluated dose-limiting toxicities (DLTs) in cycles 1 and 2. Once < 2/6 patients experienced a DLT, that dose level was expanded to evaluate feasibility over 4 cycles. Results: The study accrued 424 treated patients. For regimen 1, continuous (Reg1c) the maximum tolerated dose (MTD) was 250mg veliparib BID but the feasible dose was found to be 150mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250mg BID respectively. For Reg2c the MTD and feasible dose were the same at 150mg BID. For Reg2i the MTD and feasible dose were 250 and 150mg BID respectively. For Reg3c the MTD and feasible dose are both 150mg BID and for Reg3i, the MTD was 400mg BID and the feasible dose felt to be 300mg BID. Median PFS by residual disease and BRCA status is: (Positive residual disease) 14.6, 19.1 and 16.9 months for BRCA+, BRCAwt and BRCA ukn respectively. For no gross residual disease the PFS is NR, 34.2 and 24.5 months respectively. Conclusions: Given the difficulty with toxicity not defined as a DLT, the RP2D for all regimens is veliparib 150mg BID. This data informed the dose that moved into the phase III trial GOG 3005/Velia: NCT02470585. Velia also incorporated maintenance veliparib instead of maintenance bevacizumab among all high grade serous patients (BRCA+ and wt). These results will determine utilization of veliparib in this space. Clinical trial information: NCT00989651.

scholarly journals Downregulation of RIF1 Enhances Sensitivity to Platinum-Based Chemotherapy in Epithelial Ovarian Cancer (EOC) by Regulating Nucleotide Excision Repair (NER) Pathway

2018 ◽  
Vol 46 (5) ◽  
pp. 1971-1984 ◽  
Author(s):  
Yong-Bin Liu ◽  
Ying Mei ◽  
Zheng-Wen Tian ◽  
Jing Long ◽  
Chen-Hui Luo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Online Databases ◽  
Platinum Based Chemotherapy ◽  
Nucleotide Excision ◽  
Induced Apoptosis ◽  
Platinum Chemotherapy

Background/Aims: Rap1 interacting factor 1 (RIF1) was deemed to be involved in replication timing regulation and DNA damage response. However, little is known about the role of RIF1 in malignancies. Thus, this study aimed to investigate whether the expression of RIF1 is relevant to the response of epithelial ovarian cancer (EOC) patients to cisplatin chemotherapy and its underlying mechanism. Methods: Immunohistochemistry was used for detecting the expression of RIF1 in 72 human ovarian cancer tissues followed by association analysis of RIF1 expression with patients’ responses to platinum-based chemotherapy. The survival analysis of ovarian patients based on platinum chemotherapy was analyzed using online databases. RNA interference of RIF1 was carried out in OVCAR3 and A2780 cell lines, to determine the effect of lacking RIF1 expression on cellular responses to cisplatin by using MTS assay. The nucleotide excision repair (NER) capacity of these cells was assessed by using host-cell reactivation and UV sensitivity assay. Western Blot analysis was carried out to determine the effect of RIF1 on the proteins of NER and apoptosis signaling pathway by using RIF1 knockdown cells. BALB/c nude mice model was used for detection of response to cisplatin in vivo. Results: RIF1 expression was significantly associated with the response of ovarian patients to platinum-based chemotherapy (P< 0.01). In cohorts from online databases, high expression of RIF1 was associated with higher mortality of EOC patients based on platinum chemotherapy (P < 0.01). RIF1 knockdown increased sensitivity to cisplatin in EOC in vitro and in vivo. Deletion of RIF1 impaired the NER activity by inhibiting the NER proteins in ovarian cancer cells. Besides, knockdown of RIF1 enhanced cisplatin-induced apoptosis. Conclusions: RIF1 plays an important role in regulating the expression of NER proteins, which in turn contributes to cellular response to cisplatin and EOC patients’ response to platinum-based chemotherapy. RIF1 knockdown also promotes cisplatin-induced apoptosis. RIF1 may serve as a novel biomarker for predicting platinum-based chemosensitivity and the prognosis of EOC patients.

Impact of antibiotic treatment during platinum chemotherapy on survival and recurrence in women with advanced epithelial ovarian cancer

2020 ◽  
Vol 159 (3) ◽  
pp. 699-705
Author(s):  
Laura M. Chambers ◽  
Michelle Kuznicki ◽  
Meng Yao ◽  
Anna Chichura ◽  
Morgan Gruner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Antibiotic Treatment ◽  
Advanced Epithelial Ovarian Cancer ◽  
Platinum Chemotherapy

scholarly journals Epidemiology of epithelial ovarian cancer: a tertiary hospital based study in Goa, India

2017 ◽  
Vol 6 (6) ◽  
pp. 2541 ◽  
Author(s):  
Dweep Jindal ◽  
Mrinalini Sahasrabhojanee ◽  
Manjusha Jindal ◽  
Joachim D’Souza
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Multivariate Regression Analysis ◽  
Tertiary Hospital ◽  
Age At Diagnosis ◽  
Therapeutic Approaches ◽  
Stage Of Disease ◽  
Ovarian Epithelial Cancer ◽  
Independent Risk Factors ◽  
Platinum Chemotherapy

Background: Ovarian malignancy is seventh most common cancer in women globally. With increase in longevity, the incidence of epithelial ovarian cancer is increasing and its etiopathology remains unknown. We present preliminary epidemiological findings to help prioritize research.Methods: Present epidemiological study is retrospective, descriptive study over two years. The collected data was analyzed using SPSS software for overall survival, with respect to stage of disease and histopathology type. Multivariate analysis was done to know independent risk factors.Results: 114 cases of primary ovarian epithelial cancer were analyzed. Patients' mean age at diagnosis was 52.1±8.96 years (median=52). 52.6% patients had stage III disease at first visit. Serous adenocarcinoma (85.05%) was the most prevalent type of histopathology followed by mucinous (7.1%), clear cell (6.1%) and Endometroid carcinoma (1.75%). Surgery followed by combination of taxane and platinum chemotherapy was first line treatment in 35%. The mean age at diagnosis was more with advancing stage (stage one 44±9.53 and stage four 55.35±9.74 years) but it was not statistically significant (p=0.098) Advancing age demonstrated poor survival (log-rank p=0.05) but survival was not significantly different in relation to histopathology (log-rank =0.629). On multivariate regression analysis age of patient (p=0.004), and stage of disease (p=0.005) were found to be independent risk factors while histopathology was not an independent risk factor (p=0.688) for survival.Conclusions: Research should be aimed to find tools for screening and early diagnosis as well as better therapeutic approaches for advanced epithelial ovarian cancer.

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